CN112641918A

CN112641918A - Application of ginger powder in preparation of medicine for treating viral influenza

Info

Publication number: CN112641918A
Application number: CN202110055213.4A
Authority: CN
Inventors: 林成海; 万晓兰
Original assignee: Fujian Longzhi Biotechnology Co ltd
Current assignee: Fujian Longzhi Biotechnology Co ltd
Priority date: 2020-10-09
Filing date: 2021-01-15
Publication date: 2021-04-13

Abstract

The invention discloses application of ginger powder in preparation of a medicament for treating viral influenza, and particularly relates to application of ultrafine crushed ginger powder in preparation of a medicament for treating H1N1 viral influenza. The ginger powder can obviously improve the symptoms of the H1N1 viral influenza.

Description

Application of ginger powder in preparation of medicine for treating viral influenza

Technical Field

The invention relates to application of ginger powder in preparing a medicament for treating viral influenza, in particular to application of ultrafine crushed ginger powder in preparing a medicament for treating H1N1 viral influenza.

Background

Viral influenza, also known as upper respiratory infection, is a common disease. When the immunity of the body is low, external viruses can invade the human body through the upper respiratory tract to cause viral influenza. Since viruses exist in respiratory tracts of patients, when the patients sneeze or cough, the viruses are infected by droplets ejected by the patients, so that the viral cold is extremely high in infectivity and difficult to control, and the virus causes great harm to human beings.

Although many medicaments are used for treating viral influenza at present. However, due to high incidence rate and high infectivity of viral influenza, the development of new drugs for treating viral influenza is still urgently needed.

Disclosure of Invention

According to one aspect of the invention, the invention provides application of ginger powder in preparing a medicament for treating viral influenza.

According to some embodiments of the invention, the viral cold is an H1N1 viral cold.

According to some embodiments of the invention, the viral cold is an H1N1 FM1 viral cold.

According to some embodiments of the invention, the ginger powder is an ultra micro ground ginger powder.

According to some embodiments of the invention, the ginger powder is administered at a concentration of 50mg/kg to 800 mg/kg.

According to some embodiments of the invention, the ginger powder is formulated at a concentration of 2 mg/ml to 40 mg/ml.

According to some embodiments of the invention, the ginger powder is administered orally.

According to one aspect of the present invention, there is provided ginger powder for treating viral influenza.

Definition of

Ginger powder

The ginger powder in the present invention is ginger powder prepared using an ultra-micro pulverization method according to patent application 201710859699.0, "method for preparing ginger powder by ultra-micro pulverization", which is incorporated herein by reference in its entirety.

The ginger powder prepared by the superfine grinding method in the invention is also called as "dietary raw powder" or SSF.

Viral cold

Viral colds are of various types, including but not limited to the common cold, acute viral laryngitis or pharyngitis, acute herpangina, pharyngoconjunctivitis. Wherein the common cold is mainly caused by rhinovirus, coronavirus, parainfluenza virus, coxsackievirus, echovirus, respiratory syncytial virus and the like; acute viral laryngitis or pharyngitis is mainly caused by rhinovirus, adenovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, enterovirus and the like; acute herpangina is mainly caused by coxsackie virus a; the pharyngoconjunctivitis is mainly caused by adenovirus and Coxsackie virus.

H1N1 virus

The H1N1 virus is an influenza a virus, one of the most commonly infected influenza viruses in humans. The name of H1N1 comes from two antigenic names on the virus, namely "H" refers to Hemagglutinin (Hemagglutinin) and "N" refers to Neuraminidase (Neuraminidase). H1N1 is a minus-strand single-stranded RNA virus. The H1N1 strain is H1N1 type FM1 strain, which is provided by the institute of pharmaceutical and biological technology of Chinese academy of medical sciences, is preserved by passage of experimental research units, and has scientific research quality.

According to some embodiments of the invention, the ginger powder is administered at a concentration of 2 mg/ml to 40 mg/ml.

Method for treating diseases and pharmaceutical application

In accordance with one aspect of the present invention, a method of treating a viral cold is disclosed, the method comprising administering ginger powder to a patient.

According to some embodiments of the invention, the ginger powder is a commercially available ginger powder.

According to one aspect of the invention, the invention discloses application of ginger powder in preparing a medicament for treating viral influenza.

Concentration of

According to certain embodiments of the invention, the ginger powder is administered in a concentration of 50mg/kg to 800mg/kg, such as 50mg/kg to 700mg/kg, 50mg/kg to 600mg/kg, 50mg/kg to 500mg/kg, 50mg/kg to 400mg/kg, 50mg/kg to 300mg/kg, 50mg/kg to 200mg/kg, 50mg/kg to 150mg/kg, 50mg/kg to 100mg/kg, 100mg/kg to 800mg/kg, 100mg/kg to 700mg/kg, 100mg/kg to 600mg/kg, 100mg/kg to 500mg/kg, 100mg/kg to 400mg/kg, 100mg/kg to 300mg/kg, 100mg/kg-200mg/kg, 100mg/kg-150mg/kg, 150mg/kg-800mg/kg, 150mg/kg-700mg/kg, 150mg/kg-600mg/kg, 150mg/kg-500mg/kg, 150mg/kg-400mg/kg, 150mg/kg-300mg/kg, 150mg/kg-200mg/kg, 200mg/kg-800mg/kg, 200mg/kg-700mg/kg, 200mg/kg-600mg/kg, 200mg/kg-500mg/kg, 200mg/kg-400mg/kg, 200mg/kg-300mg/kg, 300mg/kg-800mg/kg, 300mg/kg-700mg/kg, 300mg/kg-600mg/kg, 300mg/kg-500mg/kg, 300mg/kg-400mg/kg, 400mg/kg-800mg/kg, 400mg/kg-700mg/kg, 400mg/kg-600mg/kg, 400mg/kg-500mg/kg, 500mg/kg-800mg/kg, 500mg/kg-700mg/kg, 500mg/kg-600mg/kg, 600mg/kg-800mg/kg, 600mg/kg-700mg/kg or 700mg/kg-800 mg/kg. According to certain embodiments of the invention, the ginger powder is administered at a concentration of 50mg/kg, 100mg/kg, 150mg/kg, 200mg/kg, 250mg/kg, 300mg/kg, 350mg/kg, 400mg/kg, 450mg/kg, 500mg/kg, 550mg/kg, 600mg/kg, 650mg/kg, 700mg/kg, 750mg/kg or 800 mg/kg.

According to some embodiments of the invention, the low dose of ginger powder is 150 mg/kg. According to some embodiments of the invention, the medium dose of ginger powder is 300 mg/kg. According to some embodiments of the invention, the high dose of ginger powder is 600 mg/kg.

According to some embodiments of the invention, the ginger powder is formulated at a concentration of 2 mg/ml to 40 mg/ml, such as 2 mg/ml to 35 mg/ml, 2 mg/ml to 30 mg/ml, 2 mg/ml to 25 mg/ml, 2 mg/ml to 20 mg/ml, 2 mg/ml to 15 mg/ml, 2 mg/ml to 10 mg/ml, 2 mg/ml to 5 mg/ml, 5 mg/ml to 40 mg/ml, 5 mg/ml to 35 mg/ml, 5 mg/ml to 30 mg/ml, 5 mg/ml to 25 mg/ml, or, 5 mg/ml-20 mg/ml, 5 mg/ml-15 mg/ml, 5 mg/ml-10 mg/ml, 10 mg/ml-40 mg/ml, 10 mg/ml-35 mg/ml, 10 mg/ml-30 mg/ml, 10 mg/ml-25 mg/ml, 10 mg/ml-20 mg/ml, 10 mg/ml-15 mg/ml, 15 mg/ml-40 mg/ml, 15 mg/ml-35 mg/ml, 15 mg/ml-30 mg/ml, 15 mg/ml-25 mg/ml, and, 15 mg/ml-20 mg/ml, 20 mg/ml-40 mg/ml, 20 mg/ml-35 mg/ml, 20 mg/ml-30 mg/ml, 20 mg/ml-25 mg/ml, 25 mg/ml-40 mg/ml, 25 mg/ml-35 mg/ml, 25 mg/ml-30 mg/ml, 30 mg/ml-40 mg/ml, 30 mg/ml-35 mg/ml or 35 mg/ml-40 mg/ml. According to some embodiments of the invention, the ginger powder is formulated at a concentration of 2 mg/ml, 5 mg/ml, 10 mg/ml, 15 mg/ml, 20 mg/ml, 25 mg/ml, 30 mg/ml, 35 mg/ml, 40 mg/ml.

Pharmaceutical composition and kit

The term "pharmaceutical composition" means a mixture containing a therapeutically effective amount of one or more of the compounds and pharmaceutically acceptable tautomers, solvates, hydrates or salts thereof, together with other pharmaceutically acceptable carriers. The compounds are formulated into pharmaceutical compositions for more convenient administration to a subject.

The terms "kit" or "kit" are used interchangeably in this application. Kits comprising a therapeutically effective amount of the therapeutic agent or pharmaceutical composition are disclosed. According to certain embodiments of the present application, the kit further comprises one or more additional therapeutic agents. According to certain embodiments of the present application, the kit further comprises instructions for use. According to certain embodiments of the present application, the kit further comprises a device for the respective mode of administration, such as, but not limited to, a needle.

Dosage forms

The ginger powder can be prepared into any pharmaceutically acceptable dosage form, including but not limited to tablets, oral agents, medicinal granules, injections, liposomes, targeted drug injections, pills, capsules, granules, powders, suppositories, powders, ointments, patches, injections, solutions, suspensions, sprays, lotions, drops, liniments and the like. The pharmaceutical compositions may be prepared in dry powder form and mixed with sterile water or buffer prior to administration to prepare solutions. The pH of the buffer is generally 3 to 11, preferably 5 to 9, more preferably 7 to 8.

The terms "administering", "administering" or "administering" refer to administering a dose of a compound or pharmaceutical composition to a subject by a suitable mode of administration.

The "mode of administration" includes, but is not limited to, oral administration, intravenous administration, intrarespiratory administration, sublingual administration, topical administration, intramuscular administration, intraocular administration, transdermal absorption, parenteral administration, intraperitoneal administration, vaginal administration, buccal administration, rectal administration and the like, and any mode of administration known in the art. One skilled in the art will appreciate that the mode of administration to a subject will depend on a number of factors including the location of the disease, the age of the subject, the severity of the disease, and the components of the pharmaceutical composition, among others.

Advantageous effects

The beneficial effects of the invention include:

1. under the existing infection dosage, the medium-dosage and low-dosage groups of the dietary raw powder have certain protective effects on weight gain and life prolongation, the average weight of 2-6 days is obviously higher than that of a virus group and a ribavirin group, and the survival days are respectively prolonged by 10.6 percent and 13.3 percent compared with the virus group.

2. Survival rates of the medium dose and the low dose of the dietary raw powder in 7 days (last administration) are both 66.7 percent and are improved by 33.4 percent compared with the virome.

3. The survival rates of the dietary raw powder medium dose and the dietary raw powder low dose within 9 days (two days after stopping the medicine) are 16.6 percent and 33.3 percent respectively, which are obviously higher than those of a virus group (0.0 percent) and a ribavirin group (0.0 percent).

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

When "about" is used in this application to modify a numerical value, it is meant that the numerical value may fluctuate within a range of ± 10%, ± 9%, ± 8%, ± 7%, ± 6%, ± 5%, ± 4%, ± 3%, ± 2% or ± 1%.

The use of the terms "a" and "an" and "the" and similar referents in the context of describing the application (including the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms "comprising," "having," "including," and "containing" as used herein are to be construed as open-ended terms (i.e., "including, but not limited to") unless otherwise indicated herein or otherwise clearly contradicted by context. All methods described herein can be performed in any suitable order, as understood by those skilled in the art, unless otherwise indicated herein or otherwise clearly contradicted by context.

All patents, patent applications, and references cited in this application are incorporated by reference into this application in their entirety to the same extent as if each individual reference were individually incorporated by reference. In the event of a conflict between the present application and the references provided herein, the present application shall control.

Drawings

Figures 1, 2 and 3 show that under the existing infection dosage, the medium-dosage and low-dosage groups of the dietary raw powder have a certain protective effect on weight gain, and the average weight of 2-6 days is obviously higher than that of the virus group and ribavirin group.

Figures 4 and 5 show that the survival of mice after infection (observed on day 10) was 66.7% at 7 days (last dose) and increased by 33.4% over the virus group. The survival rates of the dietary raw powder medium dose and the dietary raw powder low dose within 9 days (two days after stopping the medicine) are 16.6 percent and 33.3 percent respectively, which are obviously higher than those of a virus group (0.0 percent) and a ribavirin group (0.0 percent).

Detailed Description

The present invention will be further illustrated with reference to specific examples, but the scope of the present invention is not limited to these examples.

Example 1: H1N1 infected animals

In this example, the detailed mouse breeding method and H1N1 infection method are described in article "protective action of infantile common cold granules on H1N1 influenza virus induced acute lung injury" of juhai swallow, xian lifeng, steinerong, juanjuhui and zhi (Chinese patent medicine "3/42/3/2020). This reference is incorporated by reference into this application in its entirety.

The virus strain influenza A1 (H1N1) mouse lung adapted strain FM1 (batch number 20171002) is provided by the institute of pharmaceutical and biotechnology of Chinese academy of medical sciences, is preserved by passage in the research room (BSL-2 level), is already put on record in the room, and has the experimental qualification for operating influenza virus.

Babl/C mice, SPF grade, males, initial body weight 17-18g, purchased from Spirol-BikC laboratory animals Co., Ltd. (certification: 20180006017239) were used in this example.

Influenza A virus H1N1 FM1 mouse lung adapted strain is diluted to the concentration of about 2 XLD 50 (equivalent to 1X 10 of stock solution) by 1640 culture medium^－5Diluted) virus solution, and stored in ice bath. Except the normal group, each of the other groups was anesthetized and then infected by nasal drip, with 15. mu.L each of the left and right nostrils for 30. mu.L/patient.

Example 2: ginger powder for treating animal weight change after animal viral influenza

Mice were randomly divided into normal group, virus control group, positive drug control group (Rib group) and ginger powder low, medium and high dose groups according to body mass. In the figure, the ginger powder is also called as dietary raw powder or SSF.

Accurately weighing the medicine according to dosage, adding 0.5% CMC, preparing to corresponding concentration, and performing ultrasonic dissolution/suspension for 15 min. CMC is Carboxymethyl Cellulose (CMC), a water-soluble Cellulose ether obtained by chemically modifying natural Cellulose.

Normal group mice were given 0.5% CMC; virus control group was given 0.5% CMC; the positive drug control group is administered with ribavirin at 0.25 g/kg; the low, medium and high dosage of ginger powder are respectively 150mg/kg, 300mg/kg and 600 mg/kg.

The first administration time was 2 hours after nasal drip infection with H1N1 FM1 virus, and the subsequent administration intervals were 24 hours. The oral gavage is used for administration once a day, 8 times of administration (0-7 days) are carried out, the administration is stopped, and 14 days are observed.

Survival rate experiments were performed on mice, body weights were weighed daily, and mice were observed for mortality and recorded.

The change in body weight of the mice is shown in table 1 and fig. 1.

Table 1: mouse weight change table

The results in table 1 and fig. 1 show that under the existing infection dosage, the medium-dosage and low-dosage groups of the dietary raw powder have certain protective effects on weight gain and life prolongation, the average weight of 2-6 days is obviously higher than that of the virus group and ribavirin group, and the survival days are respectively prolonged by 10.6 percent and 13.3 percent compared with the virus group.

This example illustrates that the average body weight of the medium-dose and low-dose groups of the dietary raw powder is significantly higher than that of the virus group and ribavirin group in 2-6 days under the existing infection dose; however, in the high dose group, the body weight was significantly lower than that in the virus group at 2-5 days.

Example 3: ginger powder for treating animal death after animal viral influenza

The death of animals after the treatment of viral influenza with ginger powder is shown in table 2 and fig. 2-4.

Table 2: post-infection mouse death table (10 days observation)

The results in table 2 show that the survival rates of the medium dose and the low dose of the dietary raw powder in 7 days (last administration) are both 66.7 percent and are improved by 33.4 percent compared with the virome. The survival rates of the dietary raw powder medium dose and the dietary raw powder low dose within 9 days (two days after stopping the medicine) are 16.6 percent and 33.3 percent respectively, which are obviously higher than those of a virus group (0.0 percent) and a ribavirin group (0.0 percent).

Fig. 2 and 3 are mouse body weight-time scattergrams from which the body weight of mice at different times and different intervention modalities can be clearly observed. The results in figure 2 show that the medium-dose and low-dose groups of the dietary raw meal show obvious effects on the aspect of improving the body weight of mice and show dose correlation. The average body weight of 0-4 days is obviously higher than that of the virus group and the ribavirin group; however, the high dose group was not good for body weight, and the body weight was significantly lower in 0-4 days than in the virus group.

The results in fig. 3 show that the medium-dose and low-dose groups of the dietary raw meal show obvious effects on the aspect of improving the body weight of mice and show dose correlation. The average body weight of 5-9 days is obviously higher than that of the virus group and the ribavirin group.

FIG. 4 graph of mouse death after infection (observed on day 10) and the effect on the survival protection of influenza virus infected mice was observed. Under the existing infection dosage, the medium-dosage and low-dosage groups of the dietary raw powder have a certain protection effect on life extension, the survival days of 2-6 days are respectively prolonged by 10.6% and 13.3% compared with the virus groups, the survival rates of 7 days (last administration) are both 66.7%, the survival rates of 9 days (two days after drug withdrawal) are both 16.6% and 33.3%, and the survival rates are remarkably higher than those of the virus group (0.0%) and the ribavirin group (0.0%).

This example shows that survival rates of the medium and low doses of the dietary raw meal are 66.7% in 7 days (last administration), which is 33.4% higher than that of the virus group. The survival rates of the dietary raw powder medium dose and the dietary raw powder low dose within 9 days (two days after stopping the medicine) are 16.6 percent and 33.3 percent respectively, which are obviously higher than those of a virus group (0.0 percent) and a ribavirin group (0.0 percent). However, the high dose group showed some toxicity, resulting in a survival rate of mice in 6-8 days that was slightly lower than that of the virus group.

Example 4: animal average survival contrast after treatment of animal viral influenza with ginger powder

The average survival ratio of animals after the ginger powder treats the viral influenza of the animals is shown in table 3 and figure 5.

Table 3: average survival comparison table

The results in table 3 show that the survival rates of the medium dose and the low dose of the dietary raw powder in 7 days (last administration) are both 66.7 percent and are improved by 33.4 percent compared with the virome. The survival rates of the dietary raw powder medium dose and the dietary raw powder low dose within 9 days (two days after stopping the medicine) are 16.6 percent and 33.3 percent respectively, which are obviously higher than those of a virus group (0.0 percent) and a ribavirin group (0.0 percent).

Figure 5 is a graph of survival of mice after infection. The results in fig. 5 show that the survival rates of the medium and low doses of the dietary raw powder in 7 days (last administration) are both 66.7 percent and are improved by 33.4 percent compared with the virome. The survival rates of the dietary raw powder medium dose and the dietary raw powder low dose within 9 days (two days after stopping the medicine) are 16.6 percent and 33.3 percent respectively, which are obviously higher than those of a virus group (0.0 percent) and a ribavirin group (0.0 percent).

This example shows that survival rates of the medium and low doses of the dietary raw meal are 66.7% in 7 days (last administration), which is 33.4% higher than that of the virus group. The survival rates of the dietary raw powder medium dose and the dietary raw powder low dose within 9 days (two days after stopping the medicine) are 16.6 percent and 33.3 percent respectively, which are obviously higher than those of a virus group (0.0 percent) and a ribavirin group (0.0 percent).

The invention shows that under the existing infection dosage, the medium-dosage and low-dosage groups of the dietary raw powder have certain protective effects on weight gain and life prolongation, the average weight of 2-6 days is obviously higher than that of a virus group and a ribavirin group, and the survival days are respectively prolonged by 10.6 percent and 13.3 percent compared with the virus group.

The survival rates of the ginger powder medium dose and the ginger powder low dose in 7 days (last administration) are both 66.7 percent and are improved by 33.4 percent compared with the virome. The survival rates of the ginger powder medium dose and the ginger powder low dose in 9 days (two days after drug withdrawal) are 16.6 percent and 33.3 percent respectively, and are obviously higher than those of a virus group (0.0 percent) and a ribavirin group (0.0 percent).

However, the high dose group showed some toxicity, and the body weight was significantly lower than that of the virus group in 2-5 days, which resulted in that the survival days of the mice and the survival rate at each time point were slightly lower than that of the virus group.

From the experiment, the virus of the infection is high in toxicity, and the average survival time of the positive drug ribavirin group is only prolonged by 18.5%. The middle-dose and low-dose groups of the ginger powder show obvious effects on the aspects of improving the weight of mice and prolonging the survival, and are dose-related. However, the high dose group had significant toxicity and was not good for weight and survival.

The embodiments of the present application are exemplarily described above with reference to the drawings. Those skilled in the art can easily conceive of the disclosure of the present specification that various embodiments can be appropriately modified and recombined according to actual needs without departing from the spirit of the present application. The protection scope of this application is subject to the claims of this application.

Claims

1. Application of rhizoma Zingiberis recens powder in preparing medicine for treating viral common cold is provided.

2. The use of claim 1, wherein the viral cold is an H1N1 viral cold.

3. The use of claim 2, wherein the viral cold is a H1N1 FM1 viral cold.

4. The use according to claim 1, wherein the ginger powder is an ultra micro ground ginger powder.

5. The use as claimed in claim 1, wherein the ginger powder is administered at a concentration of 50mg/kg to 800 mg/kg.

6. The use according to claim 1, wherein the ginger powder is administered orally.

7. A rhizoma Zingiberis recens powder for treating viral common cold is provided.

8. The ginger powder of claim 7, wherein the viral cold is an H1N1 viral cold.

9. The ginger powder of claim 8, wherein the viral cold is a H1N1 FM1 viral cold.

10. The ginger powder according to claim 7, wherein the ginger powder is an ultra micro ground ginger powder.